Stereoselective Synthesis of β‐(5‐Arylthiazolyl) α‐Amino Acids and Use in Neurotensin Analogues

Abstract

AbstractA series of new unnatural amino acids bearing a β‐arylthiazole side chain was synthesized by exploiting a diastereoselective alkylation starting from glycine tert‐butyl ester Schiff base with hydroxypinanone as the chiral inducer. This strategy afforded β‐arylthiazole alanines in good chemical yields and with 98 % ee. Due to their aromatic properties, these newly generated amino acids were used to prepare neurotensin (NT)[8–13] analogues by serving as replacements for the native Tyr11 residue. Incorporation of the (L)‐(+)‐(β‐phenylthiazol‐4‐yl)alanine residue at NT[8–13] position 11 improved plasma stability and selectivity towards NTS1, while also preserving native receptor binding affinity and biological activity.